Biology subjects

Monteyne, D.

Publications and source records attributed to Monteyne, D..

3 recordsLinked to original sources

bioRxiv2022

Foxe1 orchestrates thyroid and lung cell lineage divergence in mouse stem cell-derived organoids

Patterning of endoderm into lung and thyroid lineages depends upon a correct early expression of a homeobox domain-containing transcription factor, Nkx2-1. However, the gene networks distinguishing the differentiation of those lineages remain largely unknown. In the present work, by using mouse embryonic stem cell lines, single-cell RNA sequencing, and transcriptomic and chromatin accessibility profiling, we show that knockout of Foxe1 drastically impairs Nkx2-1+ cells differentiation and maturation into thyroid follicular-like cells. Concomitantly, a subset of Foxe1 null/Nkx2-1+ cells have a remarkable ability in vitro to undergo a lung epithelial differentiation program and form lung-like organoids harboring cells transcriptionally similar with mouse fetal airway and alveolar cell types. These results demonstrate, for the first time, lung lineage derivation at the expense of thyroid lineage, by a simple removal of a transcription factor, and provide insights into the intricated mechanisms of fate decisions of endodermal cell types. Highlights- Forward programming of mESCs with transient Nkx2-1 and Pax8 overexpression, followed by c-AMP treatment, leads to differentiation of functional thyroid follicles in vitro; - In absence of Foxe1, thyroid follicle-like structures, derived from mESCs, are scarce and non-functional; - Concomitantly, a subset of Nkx2-1-expressing cells generated from Foxe1KO mESCs spontaneously form lung organoids containing multiple differentiated lung cell types; - ATACseq analyses show higher chromatin remodeling in Nkx2-1-expressing cells in control compared to Foxe1KO cells, especially for genes involved in thyroid maturation and maintenance of the 3D structure of the follicle.

developmental biology↗

bioRxiv2021

Investigating the two regimes of fibrin clot lysis: an experimental and computational approach

It has been observed in vitro that complete clot lysis is generally preceded by a period of latency during which the degradation seems to be inefficient. However, this latency was merely notified but not yet quantitatively discussed. In our experiments we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average the slow regime lasts longer than the fast one, meaning that during most of the process the lysis is ineffective. We proposed a computational model in which the two regimes result from a spatially constrained kinetic of clot lysis: first the biochemical reactions take place at the outer core of the fibrin fibers composing the clot, then in the bulk resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally. Our results shed light on new insights regarding the dynamical aspects of the lysis of fibrin rich clots in a context where the timing is so critical for patient treatment and outcome. SignificanceWhile the interplay between the main components of the fibrinolytic system is well understood, some dynamical aspects of the fibrinolysis remain unclear. Notably, we observe that in vitro fibrin rich clots undergo a slow and inefficient phase of degradation when subject to endogenous fibrinolysis. In fact, it turns out that a large part of the lysis process operates in this slow regime. To explain this observation, we proposed a computational model in which the properties of the binding of the proteins change during the lysis. First plasminogen and tissue plasminogen activator bind at the surface of the fibers, resulting in a slow lysis, then in the bulk of the fibers thus speeding up the degradation of the clot..

biophysics↗

bioRxiv2021

Keratin dynamics govern the establishment of the maternal-fetal interface.

After implantation, the mouse embryo undergoes gastrulation and forms mesoderm and endoderm. Mesoderm participates in embryonic and extra-embryonic tissues including the amnion, yolk sac, chorion and allantois, the umbilical cord precursor. Extra-embryonic mesoderm is rich in intermediate filaments. Two-photon live imaging of keratin 8-eYFP knock-in embryos allowed recording nucleation and elongation of keratin filaments, which formed apical cables coordinated across multiple cells in amnion, allantois, and blood islands. Embryos lacking all keratins displayed a deflated exocoelomic cavity, a narrow thick amnion, and a short allantois, indicating a hitherto unknown role for keratin filaments in post-implantation extra-embryonic membranes morphogenesis. Single-cell RNA sequencing of mesoderm cells, microdissected amnion, chorion, and allantois provided an interactive atlas of transcriptomes with germ layer and regional information. Keratin 8high mesenchymal cells in contact with the exocoelom shared a cytoskeleton and adhesion expression profile that might explain the adaptation of extra-embryonic structures to the increasing mechanical pressure. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/438772v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@30dfe4org.highwire.dtl.DTLVardef@bb19d6org.highwire.dtl.DTLVardef@19d6758org.highwire.dtl.DTLVardef@ebd3a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗